Systems for self-healing composite materials

ABSTRACT

A composite material precursor composition includes a matrix precursor, a first plurality of capsules including a liquid polymerizer, an activator, and an accelerant. The liquid polymerizer polymerizes when in contact with the activator, and the accelerant is an accelerant for the polymerization of the liquid polymerizer. The composite material precursor may be used to form a composite material that includes a solid polymer matrix, the first plurality of capsules in the solid polymer matrix, the activator in the solid polymer matrix, and the accelerant in the solid polymer matrix.

REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/174,214 entitled “Functionalized Particles For Self-Healing CompositeMaterials” filed Apr. 30, 2009, which is incorporated by reference inits entirety.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under contract number(s)FA9550-06-1-0553 and FA9550-05-1-0346 awarded by the Air Force Office ofScientific Research MURI, and under contract number(s) DMI 0328162awarded by the National Science Foundation. The government has certainrights in the invention.

BACKGROUND

Cracks that form within materials can be difficult to detect and almostimpossible to repair. A successful method of autonomically repairingcracks that has the potential for significantly increasing the longevityof materials has been described, for example, in U.S. Pat. No.6,518,330. This self-healing system includes a material containing, forexample, solid particles of Grubbs catalyst and capsules containingliquid dicyclopentadiene (DCPD) embedded in an epoxy matrix. When acrack propagates through the material, it ruptures the microcapsules andreleases DCPD into the crack plane. The DCPD then contacts the Grubbscatalyst, undergoes Ring Opening Metathesis Polymerization (ROMP), andcures to provide structural continuity where the crack had been.

Materials used in medical implants could benefit from having autonomicself-healing properties. Failure of these materials can be harmful oreven fatal to the patient, and may require surgical intervention torepair the damage or to replace the material. In one example, fatigueand/or failure of bone cements used in artificial hip or knee implantscan result in the formation of debris particles. These particles cancontribute to aseptic loosening, in which inflammation of the naturaltissue leads to bone destruction and loosening of the prosthesis. In2004, revision surgeries performed in the U.S. to repair or replace hipor knee implants cost over $3 billion in hospitalization fees.

Bone cement based on poly(methyl methacrylate) (PMMA) has emerged as oneof the premier synthetic biomaterials in contemporary orthopedics, andis used for anchoring prostheses to the contiguous bone in cementedarthroplasties. The bone cement formulation typically includes a liquidcomponent and a solid component. The liquid component includes methylmethacrylate (MMA) monomer, and typically includes a tertiary aromaticamine accelerant such as dimethylamino-p-toluidine (DMPT) ordimethylaniline (DMA). The solid component includes a polymerizationinitiator such as benzoyl peroxide (BPO), a combination of PMMA andpoly(styrene-co-methyl methacrylate) beads, and a radiopacifier such asbarium sulfate. The liquid and solid components are mixed together justbefore use to form a grouting material that quickly sets due topolymerization of the MMA monomer.

Bone cement has a number of disadvantages. Toxicity of some of thereactants can lead to chemical necrosis. The high exotherm of thepolymerization of MMA to PMMA can lead to thermal necrosis. Weak linkzones can be formed, particularly at the bone-cement interface and atthe cement-prosthesis interface. These disadvantages can contribute toaseptic loosening and/or other complications during and/or aftersurgery, and often lead to revision surgery.

Attempts at developing a self-healing bone cement have included using apolyester matrix material; a monomer mixture containing 35 weightpercent (wt %) styrene, 35 wt % divinyl benzene and polystyrene (35 wt%); an accelerant containing cobalt (II) naphthenate and DMA; and methylethyl ketone peroxide (MEKP) as an initiator for the polymerization ofthe monomer mixture (Hegeman, A. J. Self Repairing Polymers: RepairMechanisms and Micromechanical Modeling; Master of Science thesis;University of Illinois at Urbana-Champaign: Urbana, Ill., 1997). Theseattempts have met with mixed success, and likely have suffered from aninsufficient amount of initiator in the crack plane of the damaged bonecement.

It is desirable to provide a self-healing bone cement material. It isalso desirable to provide a self-healing material in which the healingis more rapid and/or robust than in conventional self-healing materials.

SUMMARY

In one aspect, the invention provides a composite material precursorcomposition that includes a matrix precursor, a first plurality ofcapsules including a liquid polymerizer, an activator, and anaccelerant. The liquid polymerizer polymerizes when in contact with theactivator, and the accelerant is an accelerant for the polymerization ofthe liquid polymerizer.

In another aspect, the invention provides a composite material thatincludes a solid polymer matrix, a first plurality of capsules in thesolid polymer matrix, an activator in the solid polymer matrix, and anaccelerant in the solid polymer matrix. The first plurality of capsulesincludes a liquid polymerizer, and the liquid polymerizer polymerizeswhen in contact with the activator. The accelerant is an accelerant forthe polymerization of the liquid polymerizer.

In another aspect, the invention provides a composite material thatincludes a solid polymer matrix, a first plurality of capsules in thesolid polymer matrix, an activator in the solid polymer matrix, and aplurality of functionalized particles in the solid polymer matrix. Thefirst plurality of capsules includes a liquid polymerizer, and theliquid polymerizer polymerizes when in contact with the activator. Thefunctionalized particles include particles having a surface, and afunctional group immobilized on the surface of the particles. Thefunctional group includes an accelerant for the polymerization of thepolymerizer.

In another aspect, the invention provides a method of making a compositematerial that includes combining ingredients including a matrixprecursor, a first plurality of capsules including a liquid polymerizer,an activator and an accelerant; and solidifying the matrix precursor toform a solid polymer matrix. The liquid polymerizer polymerizes when incontact with the activator, and the accelerant is an accelerant for thepolymerization of the liquid polymerizer.

To provide a clear and more consistent understanding of thespecification and claims of this application, the following definitionsare provided.

The term “polymer” means a substance containing more than 100 repeatunits. The term “polymer” includes soluble and/or fusible moleculeshaving long chains of repeat units, and also includes insoluble andinfusible networks. The term “prepolymer” means a substance containingless than 100 repeat units and that can undergo further reaction to forma polymer.

The term “matrix” means a continuous phase in a material.

The term “capsule” means a hollow, closed object having an aspect ratioof 1:1 to 1:10, and that may contain a solid, liquid, gas, orcombinations thereof. The aspect ratio of an object is the ratio of theshortest axis to the longest axis, where these axes need not beperpendicular. A capsule may have any shape that falls within thisaspect ratio, such as a sphere, a toroid, or an irregular ameboid shape.The surface of a capsule may have any texture, for example rough orsmooth.

The term “on”, in the context of a particle and a functional group,means supported by. A functional group that is on a particle may beseparated from the particle by one or more other substances, such as anadhesion promoter or another functional group. The functional group mayor may not be above the particle during the formation or use of thefunctionalized particle.

The term “healing agent” means a substance that can contribute to therestoration of structural integrity to an area of a material that hasbeen subjected to damage. Examples of healing agents includepolymerizers, activators for polymerizers, accelerants, solvents, andmixtures of these.

The term “polymerizer” means a composition that will form a polymer whenit comes into contact with a corresponding activator for thepolymerizer. Examples of polymerizers include monomers of polymers, suchas styrene, ethylene, acrylates, methacrylates and dicyclopentadiene(DCPD); one or more monomers of a multi-monomer polymer system, such asdiols, diamines and epoxides; prepolymers such as partially polymerizedmonomers still capable of further polymerization; and functionalizedpolymers capable of forming larger polymers or networks.

The term “activator” means anything that, when contacted or mixed with apolymerizer, will form a polymer. Examples of activators includecatalysts and initiators. A corresponding activator for a polymerizer isan activator that, when contacted or mixed with that specificpolymerizer, will form a polymer.

The term “catalyst” means a compound or moiety that will cause apolymerizable composition to polymerize, and that is not always consumedeach time it causes polymerization. This is in contrast to initiators,which are always consumed at the time they cause polymerization.Examples of catalysts include ring opening metathesis polymerization(ROMP) catalysts such as Grubbs catalyst. Examples of catalysts alsoinclude silanol condensation catalysts such as titanates anddialkyltincarboxylates. A corresponding catalyst for a polymerizer is acatalyst that, when contacted or mixed with that specific polymerizer,will form a polymer.

The term “initiator” means a compound or moiety that will cause apolymerizable composition to polymerize and, in contrast to a catalyst,is always consumed at the time it causes polymerization. Examples ofinitiators include peroxides, which can form a radical to causepolymerization of an unsaturated monomer; a monomer of a multi-monomerpolymer system, such as a diol, a diamine, and an epoxide; and amines,which can form a polymer with an epoxide. A corresponding initiator fora polymerizer is an initiator that, when contacted or mixed with thatspecific polymerizer, will form a polymer.

The term “accelerant” means a substance that increases the rate of apolymerization reaction without being consumed.

The term “solvent”, in the context of a healing agent, means a liquidthat can dissolve another substance, and that is not a polymerizer.

The term “encapsulant” means a material that will dissolve or swell in apolymerizer and, when combined with an activator, will protect theactivator from reaction with materials used to form a solid polymermatrix. A corresponding encapsulant for a solid polymer matrix and for apolymerizer will protect an activator from reaction with materials usedto form that specific solid polymer matrix and will dissolve or swell inthat specific polymerizer.

The term “matrix precursor” means a composition that will form a polymermatrix when it is solidified. A matrix precursor may include a monomerand/or prepolymer that can polymerize to form a solid polymer matrix. Amatrix precursor may include a polymer that is dissolved or dispersed ina solvent, and that can form a solid polymer matrix when the solvent isremoved. A matrix precursor may include a polymer at a temperature aboveits melt temperature, and that can form a solid polymer matrix whencooled to a temperature below its melt temperature.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be better understood with reference to the followingdrawings and description. The components in the figures are notnecessarily to scale and are not intended to accurately representmolecules or their interactions, emphasis instead being placed uponillustrating the principles of the invention.

FIG. 1 depicts a schematic representation of a composite materialincluding capsules containing a liquid polymerizer, an activator, andfunctionalized particles.

FIG. 2 depicts the formation of a functionalized particle.

FIG. 3 depicts infrared spectra of hydroxyapatite (HA) anddimethylaminobenzyl alcohol-modified HA (m-HA).

FIG. 4 depicts TGA data for HA, dimethylaminobenzyl alcohol-modified HA(m-HA), and HA functionalized by HMDI alone and quenched with methanol.

FIG. 5 depicts dynamic DSC data for the curing reactions of a bonecement mimic containing no accelerant, m-HA as an accelerant anddimethylaniline (DMA) as an accelerant.

FIG. 6 depicts dynamic DSC data for various initiators.

FIG. 7 depicts dynamic DSC data for the polymerization of Derakane510A-40 epoxy vinyl ester resin with various initiators.

FIGS. 8A and 8B depict graphs of polymerization conversion for an epoxyvinyl ester resin using combinations of initiator VII and accelerant XII(a) and of initiator VIII and accelerant XII (b), at various accelerantconcentrations and reaction temperatures.

FIGS. 9A and 9B depicts graphs of polymerization conversion for an epoxyvinyl ester resin using various accelerant:initiator ratios ([A]:[I]) ofaccelerant XII and initiator VII (a) and of accelerant XII and initiatorVIII (b).

FIG. 10 depicts graphs of the average modulus for an epoxy vinyl esterformed versus the various accelerant:initiator ratios ([A]:[I]) used,where the accelerant was XII and the initiator was either VII (BPO) orVIII (LPO).

DETAILED DESCRIPTION

In accordance with the present invention a composite material precursorcomposition includes a matrix precursor, a first plurality of capsulesincluding a liquid polymerizer, an activator, and an accelerant. Theliquid polymerizer polymerizes when in contact with the activator, andthe accelerant is an accelerant for the polymerization of the liquidpolymerizer. The composite material precursor may be used to form acomposite material that includes a solid polymer matrix, the firstplurality of capsules in the solid polymer matrix, the activator in thesolid polymer matrix, and the accelerant in the solid polymer matrix.

In one example, a composite material includes a solid polymer matrix, afirst plurality of capsules in the solid polymer matrix, an activator inthe solid polymer matrix, and a plurality of functionalized particles inthe solid polymer matrix. The first plurality of capsules includes aliquid polymerizer, which polymerizes when in contact with theactivator. The functionalized particles include a particle having asurface, and a functional group immobilized on the surface of theparticle. The functional group is an accelerant for the polymerizationof the polymerizer.

FIG. 1 is a schematic representation of a composite material 100 thatincludes a solid polymer matrix 110, a first plurality of capsules 120in the solid polymer matrix, an activator in the solid polymer matrix,and a plurality of functionalized particles 140 in the solid polymermatrix. The first plurality of capsules 120 includes a liquidpolymerizer, which polymerizes when in contact with the activator. Theactivator may be present in optional activator particles 130.

The solid polymer matrix 110 may include a polyamide such as nylon; apolyester such as poly(ethylene terephthalate) and polycaprolactone; apolycarbonate; a polyether; an epoxy polymer; an epoxy vinyl esterpolymer; a polyimide such as polypyromellitimide (for example KAPTAN); aphenol-formaldehyde polymer such as BAKELITE; an amine-formaldehydepolymer such as a melamine polymer; a polysulfone; apoly(acrylonitrile-butadiene-styrene) (ABS); a polyurethane; apolyolefin such as polyethylene, polystyrene, polyacrylonitrile, apolyvinyl, polyvinyl chloride and poly(DCPD); a polyacrylate such aspoly(ethyl acrylate); a poly(alkylacrylate) such as poly(methylmethacrylate); a polysilane such as poly(carborane-silane); and apolyphosphazene. The solid polymer matrix 110 may include an elastomer,such as an elastomeric polymer, an elastomeric copolymer, an elastomericblock copolymer, and an elastomeric polymer blend. Self-healingmaterials that include an elastomer as the solid polymer matrix aredisclosed, for example, in U.S. Pat. No. 7,569,625. The solid polymermatrix 110 may include a mixture of these polymers, including copolymersthat include repeating units of two or more of these polymers, and/orincluding blends of two or more of these polymers.

Preferably the solid polymer matrix includes a polymer containingacrylate and/or alkyl acrylate monomer units. More preferably the solidpolymer matrix includes a polymer containing methacrylate units, andmore preferably containing methyl methacrylate units. In one example,the solid polymer matrix is poly(methyl methacrylate) PMMA.

The solid polymer matrix 110 may include other ingredients in additionto the polymeric material. For example, the matrix may contain one ormore stabilizers, antioxidants, flame retardants, plasticizers,colorants and dyes, fragrances, or adhesion promoters. An adhesionpromoter is a substance that increases the adhesion between twosubstances, such as the adhesion between two polymers. One type ofadhesion promoter that may be present includes substances that promoteadhesion between the solid polymer matrix 110 and the capsules 120,and/or between the solid polymer matrix 110 and the optional activatorparticles 130. The adhesion between the matrix and the capsules mayinfluence whether the capsules will rupture or debond when a crack isformed in the composite. To promote one or both of these forms ofadhesion, various silane coupling agents may be used. Another type ofadhesion promoter that may be present includes substances that promoteadhesion between the solid polymer matrix 110 and the polymer formedfrom the polymerizer. The adhesion between the matrix and this polymermay influence whether the composite can be healed once damage hasoccurred. To promote the adhesion between the solid polymer matrix andthe polymer formed from the healing agent, various unsaturated silanecoupling agents may be used.

The first plurality of capsules 120 isolates the liquid polymerizer inthe capsules until the composite is subjected to damage that forms acrack in the composite. Once the damage occurs, the capsules in contactwith the damaged area can rupture, releasing the liquid polymerizer intothe crack plane.

The capsules 120 have an aspect ratio of from 1:1 to 1:10, preferablyfrom 1:1 to 1:5, more preferably from 1:1 to 1:3, more preferably from1:1 to 1:2, and more preferably from 1:1 to 1:1.5. In one example, thecapsules may have an average diameter of from 10 nanometers (nm) to 1millimeter (mm), more preferably from 30 to 500 micrometers, and morepreferably from 50 to 300 micrometers. In another example, the capsulesmay have an average diameter less than 10 micrometers. Capsules havingan average outer diameter less than 10 micrometers, and methods formaking these capsules, are disclosed, for example, in U.S. PatentApplication Publication 2008/0299391 with inventors White et al.,published Dec. 4, 2008.

The capsules 120 are hollow, having a capsule wall enclosing an interiorvolume containing a liquid. The thickness of the capsule wall may be,for example, from 30 nm to 10 micrometers. For capsules having anaverage diameter less than 10 micrometers, the thickness of the capsulewall may be from 30 nm to 150 nm, or from 50 nm to 90 nm. The selectionof capsule wall thickness may depend on a variety of parameters, such asthe nature of the solid polymer matrix, and the conditions for makingand using the composite. For example, a capsule wall that is too thickmay not rupture when the interface with which it is in contact isdamaged, while a capsules wall that is too thin may break duringprocessing.

Hollow capsules may be made by a variety of techniques, and from avariety of materials. Examples of materials from which the capsules maybe made, and the techniques for making them include: polyurethane,formed by the reaction of isocyanates with a diol; urea-formaldehyde(UF), formed by in situ polymerization; gelatin, formed by complexcoacervation; polyurea, formed by the reaction of isocyanates with adiamine or a triamine, depending on the degree of crosslinking andbrittleness desired; polystyrene or polydivinylbenzene formed byaddition polymerization; and polyamide, formed by the use of a suitableacid chloride and a water soluble triamine. For capsules having anaverage diameter less than 10 micrometers, the capsule formation mayinclude forming a microemulsion containing the capsule startingmaterials, and forming microcapsules from this microemulsion.

The liquid polymerizer of the first plurality of capsules 120 mayinclude, for example, a monomer, a prepolymer, or a functionalizedpolymer having two or more reactive groups. Examples of polymerizersinclude alkene-functionalized monomers, prepolymers or polymers, whichmay form a polymer when contacted with other alkene groups. Examples ofalkene-functionalized polymerizers include monomers such as acrylates;alkylacrylates including methacrylates and ethacrylates; olefinsincluding styrenes, isoprene and butadiene; and cyclic olefins includingdicyclopentadiene (DCPD), norbornene and cyclooctadiene. Examples ofalkene-functionalized polymerizers also include diallyl phthalate (DAP),diallyl isophthalate (DAIP), triallyl isocyanurate, hexanedioldiacrylate (HDDA), trimethylol propanetriacrylate (TMPTA), and epoxyvinyl ester prepolymers and polymers.

Preferably the liquid polymerizer includes acrylate and/or alkylacrylatemonomers. Acrylate and/or alkylacrylate monomers typically have goodreactivity in free radical polymerization. The resulting polymers canhave desirable mechanical properties and have been used in a variety ofbiomedical applications. Examples of monomers include methylmethacrylate (MMA; structure I), butyl methacrylate (BMA; structure II),2,2-bis[4(2-hydroxy-3-methacryloxypropoxy)phenol]propane (Bis-GMA;structure III), trimethylolpropane trimethacrylate (TMPTMA; structureIV), and ethylene glycol dimethacrylate (EGDMA; structure V):

These monomers may be present alone or in combination with each otherand/or with another alkene functional polymerizer. One example ofanother alkene functional polymerizer is styrene (structure VI):

A combination of monofunctional monomers, such as MMA, BMA and styrene,and multifunctional monomers, such as Bis-GMA, TMPTMA and EGDMA, isexpected to be particularly useful in minimizing volume shrinkage of theliquid polymerizer and in improving polymerizer reactivity. Preferablythe polymer resulting from the polymerization of the polymerizer hasgood strength.

The first plurality of capsules 120 may further include a solvent.Examples of capsules that include a polymerizer and a solvent aredisclosed, for example, in copending U.S. patent application Ser. No.12/739,537, with inventors Caruso et al., filed Apr. 23, 2010. Thecapsules may include an aprotic solvent, a protic solvent, or a mixtureof these. Examples of aprotic solvents include hydrocarbons, such ascyclohexane; aromatic hydrocarbons, such as toluene and xylenes;halogenated hydrocarbons, such as dichloromethane; halogenated aromatichydrocarbons, such as chlorobenzene and dichlorobenzene; substitutedaromatic solvents, such as nitrobenzene; ethers, such as tetrahydrofuran(THF) and dioxane; ketones, such as acetone and methyl ethyl ketone;esters, such as ethyl acetate, hexyl acetate, ethyl phenylacetate (EPA)and phenylacetate (PA); tertiary amides, such as dimethyl acetamide(DMA), dimethyl formamide (DMF) and N-methylpyrrolidine (NMP); nitriles,such as acetonitrile; and sulfoxides, such as dimethyl sulfoxide (DMSO).Examples of protic solvents include water; alcohols, such as ethanol,isopropanol, butanol, cyclohexanol, and glycols; and primary andsecondary amides, such as acetamide and formamide.

The capsules 120 may include other ingredients in addition to the liquidpolymerizer and the optional solvent. For example, the capsules maycontain one or more solvents, stabilizers, antioxidants, flameretardants, plasticizers, colorants and dyes, fragrances, or adhesionpromoters.

The activator may be a general activator for polymerization, or acorresponding activator for a specific polymerizer present in thecomposite material. Preferably the activator is a correspondingactivator for the liquid polymerizer present in the first plurality ofcapsules 120. The activator may be a catalyst or an initiator.

The activator may be a two-part activator, in which two distinctsubstances must be present in combination for the activator to function.In one example of a two-part activator system, a correspondingpolymerizer may contain alkene-functional polymerizers. In this example,atom transfer radical polymerization (ATRP) may be used, with one of theactivator components being present with the liquid healing agent, andthe other activator component acting as the initiator. One component canbe an organohalide such as 1-chloro-1-phenylethane, and the othercomponent can be a copper(I) source such as copper(I) bipyridyl complex.In another exemplary system, one activator component could be a peroxidesuch as benzoyl peroxide, and the other activator component could be anitroxo precursor such as 2,2,6,6-tetramethylpiperidinyl-1-oxy. Thesesystems are described in Stevens et al., Polymer Chemistry: AnIntroduction, 3rd Edition; Oxford University Press, New York, (1999),pp. 184-186.

Preferably the activator is a free radical polymerization initiator.More preferably the activator is a free radical polymerization initiatorthat has low toxicity, high thermal stability and high reactivity.Examples of activators for free radical polymerization of the monomersshown above as structures I through VI include peroxide initiators.Examples of peroxide initiators include benzoyl peroxide (BPO; structureVII), lauroyl peroxide (LPO; structure VIII), methyl ethyl ketoneperoxide (MEKP; structure IX), tert-butyl peroxide (TBP; structure X),tert-butyl peroxybenzoate (TBPB; structure XI):

Table 1 below lists the toxicity, water solubility (Hatakeyama, T.;Quinn, F. Applications of Thermal Analysis; Thermal Analysis:Fundamentals and Applications to Polymer Science; 2^(nd) ed.; Wiley andSons: Chichester, England, 1994) and indicators of thermal stability forthe initiators having structures VII to XI.

TABLE 1 Properties of free radical initiators Melting Boiling 10 h RatOral LD50 Water Point Point Half Life Initiator (mg/kg) Solubility (°C.) (° C.) T (° C.) VII 7,710 <0.1 g/100 mL at 26° C. 105-106 N/A 70VIII 10,000 Insoluble 53 N/A 65 IX 484 0.1-0.5 g/100 mL at 22° C. 110N/A Not Listed X 25,000 <0.1 g/100 mL at 21° C. −40 109-110 70 XI 4,160<0.1 g/100 mL at 20° C. 8 113 103 

The toxicities of these five initiators were compared via LD50 (LethalDose, 50%) values obtained from experiments performed in rats(University of Oxford, Physical and Theoretical Chemistry Laboratory,MSDS, accessed Online June 2007; Fisher Scientific, MSDS, accessedonline June 2007). The LD50 value is the dosage of a substance requiredto kill half of a sample of test subjects. The LD50 values for sodiumcyanide (6.4 mg/kg) and ethanol (7060 mg/kg) were selected as benchmarklimits for toxicity, with sodium cyanide serving as the reference valuefor an acutely toxic compound, and ethanol serving as the point ofcomparison for a mildly toxic substance (Fisher Scientific, MSDS).

The melting points and boiling points (if applicable) of each initiatorand the temperature at which the half life of the initiator is 10 hours(10 h half life T) can indicate the thermal stabilities of these fiveinitiators. This data can be used to assess the compatibility of theseor other initiators with potential processing conditions including theconditions for microencapsulation, reaction exotherms due to curing ofthe bone cement, and higher ambient temperature in vivo. Melting andboiling points can be used to assess the phases in which the initiatorsexist at room temperature, and evaluate their suitability for thetemperatures that accompany the encapsulation process or otherprocessing conditions. Since the system is to function at ambienttemperatures of 37-38° C. in vivo and even higher temperatures duringthe curing of bone cement, an evaluation of thermal stability atelevated temperature offers insight into the suitability of apolymerization initiator for such conditions.

The activator may be present in solid form, such as crystals of theactivator. These activator particles preferably are microparticleshaving an average diameter of at most 500 micrometers. Specific examplesof pure activators in solid form include solid particles of Grubbscatalyst.

The activator may be present in optional activator particles 130. Theactivator may be present in a mixture with other ingredients, such asone or more stabilizers, antioxidants, flame retardants, plasticizers,colorants and dyes, fragrances, or adhesion promoters. The optionalparticles may be present in the form of solid particles, or as a secondplurality of capsules. Optional activator particles 130 may be helpfulin protecting the activator from the conditions required to form thecomposite 100 and/or from the conditions in which the composite will beused. For a two-part activator, one part of the activator may be in theoptional activator particles 130, and the other part of the activatormay be in the solid polymer matrix or in the first plurality of capsules120.

The optional activator particles 130 may include a mixture of anactivator and an encapsulant. These activator particles may be made by avariety of techniques, and from a variety of materials. For example,small particles or a powder of the activator may be dispersed into aliquid containing the encapsulant, followed by solidification of themixture of encapsulant and activator. These activator particlespreferably are microparticles having an average diameter of at most 500micrometers. The encapsulant preferably is soluble in, or swells in, theliquid healing agent, and is a solid at room temperature. The liquidhealing agent may dissolve the encapsulant, releasing the activator andforming a polymer. The liquid healing agent may swell the encapsulant sothat the particle can be penetrated by the liquid healing agentsufficiently to allow polymerization of a polymerizer of the liquidhealing agent upon contact with the activator. Examples of particlesthat include an activator and an encapsulant are disclosed, for example,in U.S. Pat. No. 7,566,747.

The optional activator particles 130 may include capsules, and a liquidthat includes the activator in the capsules. This second plurality ofcapsules may be as described above for the first plurality of capsules,and may include other ingredients in addition to the activator. Forexample, the second plurality of capsules may contain one or morestabilizers, antioxidants, flame retardants, plasticizers, colorants anddyes, fragrances, or adhesion promoters.

The functionalized particles 140 include particles having a surface, anda functional group immobilized on the surface of the particles. Theparticles may include an inorganic and/or an organic material. Examplesof particulate materials include carbon black, ceramic particles, metalparticles, and polymer particles. Preferably the particles includehydroxyapatite (HA). Hydroxyapatite (HA) has become widely used inorthopedic applications. Advantages of HA include its osteoconductivityand osteoinductivity, and its ability to improve the mechanicalproperties of PMMA-based bone cements without detrimental effects onstress distribution or flow of the cement.

The functional group immobilized on the surface of the particles is anaccelerant for the polymerization of the polymerizer. An accelerant is asubstance that increases the rate of a polymerization reaction withoutbeing consumed. Examples of accelerants for free radical polymerizationsinclude N,N-dimethylaniline (DMA; structure XII), 4,N,N-timethylaniline(DMT; structure XIII), and 4,4′-methylene-bis(N,N-dimethyl)aniline(MBDMA; structure XIV), below. Derivatives of these or other accelerantsmay be immobilized on the surfaces of particles.

The functionalized particles 140 may be prepared by a variety oftechniques. In one example, a monomer including an accelerant functionalgroup is polymerized on the surface of a particle. In this example, thefunctionalized particle includes a polymer on its surface, where thepolymer includes multiple accelerant functional groups. An example of amonomer including an accelerant functional group is dimethylaminobenzylmethacrylate. This method of forming functionalizing particles 140 ispreferred, since it may be possible to provide a higher density ofaccelerant functional groups than is possible with the method describedbelow. Since an immobilized accelerant may have lower mobility in areaction than the corresponding non-immobilized accelerant, a higherdensity of the accelerant functional groups may help compensate for thelower mobility.

In another example, a bifunctional group is used to link the particleand the accelerant functional group. In this example, a bifunctionallinking group such as a diisocyante is bonded to the surface of aparticle through reaction of one of the isocyanate groups with afunctional group on the surface. The remaining isocyanate group is thenreacted with a functional group of the derivative of the accelerant.FIG. 2 depicts the formation of a functionalized particle, in which aparticle 200 having a hydroxyl group on the surface is reacted withreagents to form the functionalized particle 210 including a particle212, a bifunctional linking group 214 and an accelerant functional group216. The reagents in this example included hexamethylene diisocyanate(HMDI) as the precursor to the linking group 214, dibutyltin dilaurate(DBTL) to catalyze the reaction of the HMDI with the hydroxyl-functionalHA 210, and dimethylaminobenzyl alcohol (DMOH). The DMOH reagentincludes the N,N-dimethylaniline structure that is present inaccelerants XII, XIII and XIV, and also includes a hydroxyl functionalgroup for reaction with an isocyanate group of the immobilized HMDIderivative. Thus, the accelerant functional group 216 also includes theN,N-dimethylaniline structure that is present in accelerants XII, XIIIand XIV.

FIG. 3 represents IR spectra of HA particles and of dimethylaminobenzylalcohol-modified HA particles (m-HA). The spectrum of m-HA includedpeaks near 3328 cm⁻¹, 2850-2940 cm⁻¹ and 1570-1680 cm⁻¹ which were notpresent in the spectrum of HA. These peaks correspond to —NH—, —CH₂—,—CO—NH, and —C═O amide bands, respectively, indicating grafting of theDMOH to the surface of the HA.

FIG. 4 represents graphs of weight loss as a function of temperature, asmeasured by thermogravimetric analysis (TGA), for particles of eitherHA, m-HA or HA modified with a methoxy group instead of a dimethylaminobenzyoxy group. From this data, the grafting density of DMOH on m-HA wascalculated as 0.31 grams per millimole (g/mmol).

FIG. 5 represents graphs of heat flow as a function of temperature, asmeasured by dynamic differential scanning calorimetry (DSC), forsimulated bone cement reactions. For the graph labeled “No Accelerant”,the reaction mixture included 54.1 wt % PMMA beads, 5.4 wt % initiatorVII, 40.5 wt % HA and 2 mL MMA monomer. For the graph labeled “DMA (XII)Accelerant”, the reaction mixture was identical to the first mixture,except that 0.02 mL of accelerant XII was added. For the graph labeled“m-HA Accelerant”, the reaction mixture was identical to the firstmixture, except that m-HA was used instead of HA. Based on an estimationof 6.1 wt % accelerant functional groups in every sample of m-HA, thenumber of moles of accelerant in the sample containing m-HA wascalculated to be 3.06×10⁻⁴ mol, while the number of moles of accelerantin the sample containing DMA accelerant was 1.58×10⁻⁴ mol. Compared tothe sample containing no accelerant, significant polymerizationacceleration was observed for the sample containing m-HA.

The composite material such as 100 may be self-healing. When thecomposite 100 is subjected to a crack, the liquid polymerizer from thecapsules 120 can flow into the crack, contacting the activator andaccelerant and forming a polymer. The crack faces in the solid polymermatrix 110 are thus bonded to each other or to the polymer formed in thecrack. It is desirable for the first plurality of capsules, theactivator, and the functionalized particles 140 to be dispersedthroughout the composite, so that a crack will intersect and break oneor more capsules 120, releasing the liquid polymerizer, and so that thereleased liquid polymerizer can contact the activator and the accelerantfunctional group of the functionalized particle 140.

A method of making a composite material, such as composite material 100,includes combining ingredients including a matrix precursor, a firstplurality of capsules, an activator and a plurality of functionalizedparticles. The method further includes solidifying the matrix precursorto form a solid polymer matrix. The first plurality of capsules includesa liquid polymerizer, and the activator is an activator for thepolymerizer. The functionalized particles include a particle having asurface and a functional group immobilized on the surface. Thefunctional group includes an accelerant for the polymerization of thepolymerizer. The method may further include forming the functionalizedparticles. The matrix precursor may be any substance that can form asolid polymer matrix when solidified.

In one example, the matrix precursor includes a monomer and/orprepolymer that can polymerize to form a polymer. The capsules,activator and functionalized particles may be mixed with the monomer orprepolymer. The matrix precursor may then be solidified by polymerizingthe monomer and/or prepolymer of the matrix precursor to form the solidpolymer matrix.

In another example, the matrix precursor includes a polymer in a matrixsolvent. The polymer may be dissolved or dispersed in the matrix solventto form the matrix precursor, and the capsules, activator andfunctionalized particles then mixed into the matrix precursor. Thematrix precursor may be solidified by removing at least a portion of thematrix solvent from the composition to form the solid polymer matrix.

In another example, the matrix precursor includes a polymer that is at atemperature above its melting temperature. The polymer may be melted toform the matrix precursor and then mixed with the capsules, activatorand functionalized particles. The matrix precursor may be solidified bycooling the composition to a temperature below the melt temperature ofthe polymer to form the solid polymer matrix.

The following examples are provided to illustrate one or more preferredembodiments of the invention. Numerous variations can be made to thefollowing examples that lie within the scope of the invention.

EXAMPLES Materials

Non-sintered hydroxyapatite (HA; Merck: Whitehouse Station, N.J.) wasdried at 120° C. for at least 24 h before use. Hexamethylenediisocyanate (HMDI; Sigma Aldrich: St. Louis, Mo.), dibutyltin dilaurate(DBTL, Sigma Aldrich), toluene diisocyanate (TDI; Sigma Aldrich),tert-butyl peroxide (TBP; initiator X; Sigma Aldrich), methyl ethylketone peroxide (MEKP; initiator IX; Sigma Aldrich), and tert-butylperoxybenzoate (TBPB; initiator XI; Acros: Geel, Belgium),N,N-dimethylaniline (DMA; accelerant XII; Sigma Aldrich),4,N,N-timethylaniline (DMT; accelerant XIII; Fluka), and4,4′-methylene-bis(N,N-dimethyl)aniline (MBDMA; accelerant XIV; Acros),2,2-bis[4(2-hydroxy-3-methacryloxypropoxy)phenol]propane (Bis-GMA;monomer III; Sigma Aldrich), trimethylolpropane trimethacrylate (TMPTMA;monomer IV; Sigma Aldrich) and ethylene glycol trimethacrylate (EGDMA;monomer V; Sigma Aldrich) were used as-received. Benzoyl peroxide (BPO;initiator VII; Sigma Aldrich) and lauroyl peroxide (LPO; initiator VIII;Sigma Aldrich) were ground into a fine powder before use. The resinDerakane® 510A-40 Epoxy Vinyl Ester (EVE) was obtained from Ashland Inc.(Covington, Ky.) and used as received.

Example 1 Functionalization of Hydroxyapatite

Hexamethylene diisocyanate (HMDI) was used as the linker to tetherdimethylaminobenzyl alcohol (DMOH) to the hydroxyl groups present on thesurface of HA particles. The functionalization of HA particles followedestablished procedures (Liu, Q.; de Wijn, J. R.; van Blitterswijk, C.A., Journal of Biomedical Materials Research 1998, 40, 257). HA (5 g),dry DMF (75 mL), DBTL (0.075 mL) and HMDI (2.5 mL) were allowed to stirin a 500 mL round bottom flask for 8 h at 55° C. under N₂. DMOH (2 mL)or methanol was then added and the mixture was kept under the sameconditions for an additional 5 h. The functionalized HA powder wasseparated by centrifugation and washed 3 times each with DMF and ethanolsuccessively. The surface functionality of DMOH-modified hydroxyapatite(m-HA) was analyzed by infrared (IR) spectroscopy, and their IR spectraare compared in FIG. 3.

The grafting efficiency of m-HA was estimated from TGA results bycomparing the mass loss when HMDI alone was grafted to HA and quenchedwith methanol. The TGA graphs are depicted in FIG. 4. Assuming the massloss in the product was due to the HMDI-CH₃OH grafting, the number ofmoles of HMDI grafted per gram HA can be calculated. Since HMDI wasreacted with HA for the same period of time and under the sameconditions in the synthesis of m-HA prior to addition of DMOH, thegrafting efficiency of the DMOH to HA was calculated as a function ofthe number of moles of HMDI grafted to HA according to the followingequation (Liu et al.):G=W/Nwhere G is the grafting efficiency of DMOH, W is the mass of the graftedDMOH per gram of HA, and N is the number of moles of HMDI coupled to HA.Organic mass loss for the HMDI-CH₃OH functionalized HA was 4.6 wt %,corresponding to 3.9 wt % from the HMDI moiety and 0.7 wt % from themethoxy moiety. This mass loss was equivalent to 0.2 mmol HMDI per gramof HA. Total mass loss for m-HA was 10 wt %, from which 3.9 wt % likelyis due to the HMDI moiety and the remaining 6.1 wt % likely is from theDMOH moiety. The calculated grafting density for DMOH was therefore 0.31g/mmol.

Example 2 Analysis of Effect of Functionalized HA on Polymerization

The ability of m-HA particles to serve as an accelerant was evaluated ina simulated bone cement sample in which the accelerant was replaced bym-HA. Three samples, each containing 54.1 wt % PMMA beads, 5.4 wt %initiator VII, and 40.5 wt % HA were prepared. m-HA was used in one ofthe samples in the place of regular HA. MMA (2 mL) was then added toeach sample, and DMA (0.02 mL) was added to one of the samplescontaining regular HA. The curing kinetics for each sample were thenevaluated by dynamic differential scanning calorimetry (DSC) (25-200° C.at 10° C./min).

Compared to the sample containing no accelerant, significantpolymerization acceleration was observed for the sample containing m-HA(FIG. 5). However, the rate of acceleration was slower than for thesample containing liquid DMA. Based on an estimation of 6.1 wt % DMOH inevery sample of m-HA, the number of moles of accelerant in the sampleactivated by m-HA was calculated to be 3.06×10⁻⁴ mol, while the numberof moles of accelerant in the sample containing DMA was 1.58×10⁻⁴ mol.One possible reason for the difference in activities observed betweenthe two methods of acceleration may be the lack of mobility of thetethered accelerant molecules in the case of m-HA acceleration.

Example 3 Analysis of Thermal Stability of Initiators

The thermal behavior of each initiator was evaluated by dynamicDifferential Scanning Calorimetry (DSC) experiments performed on aDSC821 instrument (Mettler-Toledo). The temperature range analyzed was25° C.-300° C., with a heating rate of 10° C./min. Dynamic experimentswere performed under nitrogen atmosphere, and all DSC experiments wereperformed in 40 μL aluminum crucibles. Average sample sizes were5.66±2.66 mg for as-received samples and 2.26±0.85 mg for groundsamples. Three trials were performed for each initiator. FIG. 6 depictsdynamic DSC data for initiators VII to XI, and Table 2 lists the averagetotal heat and standard deviations for relevant thermal transitions aswell as average onset temperatures.

TABLE 2 Thermal properties of free radical initiators Heat of Total HeatAverage Decomposition 25° C.-300° C. Onset T Initiator (kJ/mol) (kJ/mol)(° C.) VII N/A 295.1[6.6] 109.1[0.1] VIII  277.5[15.4] 192.2[9.4] 85.8[0.3] IX 107.7[8.3] 107.7[8.3] 128.1[4.8] X N/A −49.4[3.3]109.2[1.0] XI 214.8[0.2] 214.8[0.2]  112.0[13.7]

In general, the onset temperature of a thermal event is defined as theintersection between the tangent to the maximum rising slope of a DSCcurve and the extrapolated sample baseline. A lower onset temperature ofdecomposition suggests more facile homolytic cleavage of peroxideinitiators. The endotherms displayed by initiators VIII and X correspondto the heat of fusion (VIII) or heat of vaporization (X) (FIG. 6, Table2). While initiator X exhibited a single thermal event, VIII exhibiteddistinct events corresponding to melting and decomposition respectively.Initiator X was observed to boil, but no decomposition was observed upto 300° C. In the case of VII, decomposition occurred adjacent tomelting, and thus the heat of fusion could not be measured independentlyof the heat of decomposition. The data suggests that initiators IX and Xare the most thermally stable of the initiators selected. While VII andVIII were the least thermally stable of selected initiators, their onsettemperature for decomposition was high enough that they are not expectedto decompose at processing and application temperatures for aself-healing bone cement.

Example 4 Analysis of Reactivity of Initiators

The reactivities of the initiators with Derakane® 510A-40 epoxy vinylester, a standard acrylic resin, were compared in the presence andabsence of accelerants. The total heat of polymerization of the epoxyvinyl ester resin with each initiator was obtained by dynamic DSCevaluations of 11.80±3.56 mg samples of epoxy vinyl ester containinginitiator (4.13×10⁻⁴ mol/g). Initiators were stirred into the resin for5 minutes at 1,000 RPM using a mechanical stirrer prior to loading thesample into the DSC. To evaluate the reactivity of these initiators withvarious accelerants, the accelerants were added to separate resinsamples already containing initiators at varying concentrations. DynamicDSC evaluations were performed on 21.92±7.44 mg sample sizes using twoconcentration combinations of initiator and accelerant (4.13×10⁻⁴ mol/gof initiator with 8.25×10⁻⁵ mol/g of accelerant, and 8.25×10⁻⁵ mol/g ofinitiator with 4.13×10⁻⁴ mol/g of accelerant). Samples with liquidaccelerant were prepared by mixing initiator and resin for 5 minutes at1,000 RPM, then adding accelerant by pipette, stirring for 15 seconds at1,000 RPM, and loading the sample into the DSC within 118±20 secondsafter addition of accelerant. For experiments with the solid accelerant(4,4′-methylene-bis(N,N-dimethyl aniline) that could not be added bypipette, initiator and accelerant were stirred into EVE separately andthe two parts were mixed for 15 seconds just prior to loading the sampleinto the DSC. Samples were loaded within 103±9 seconds after combiningand stirring the separate initiator and accelerant solutions together.Three trials were performed for each initiator. FIG. 7 depicts dynamicDSC data for the polymerization of Derakane 510A-40 epoxy vinyl esterresin with initiators VII to XI, and Table 3 lists the average totalheat of polymerization and standard deviations, as well as average onsettemperatures.

TABLE 3 Polymerization properties of free radical initiators Heat ofHeat of Polymerization Polymerization Average 25° C.-300° C. 25° C.-300°C. Onset Initiator (J/g) (kJ/mol) T (° C.) VII 240.4[9.7] 56.2[2.3]102.0[1.0] VIII 251.0[7.6] 100.1[3.0]   94.5[2.7] IX 234.4[8.8]49.3[2.3] 111.1[1.3] X  50.5[13.8]  7.4[2.0] 171.1[0.5] XI  168.1[14.5]32.6[2.8] 135.0[1.3]

As expected, in the absence of accelerants, the average onsettemperatures for polymerization of the epoxy vinyl ester resin closelymirrored the average onset temperatures for decomposition, withinitiator VIII exhibiting the lowest average onset temperature forpolymerization at 94.5±2.7° C. and X exhibiting the highest at 171±0.5°C. (FIG. 7, Table 3).

Example 5 Isothermal Analysis of Initiators

To simulate the reactivity of various combinations of initiator andaccelerant at body temperature, isothermal DSC experiments wereperformed at 38° C. Two additional temperatures (25° C. and 50° C.) wereselected to facilitate more comprehensive evaluation of the temperaturedependence of the initial rate of polymerization and the degree ofmonomer conversion. The isothermal experiments were performed at 25° C.,38° C., and 50° C., respectively, for 120 minutes on samples containinga mixture of Derakane® 510A-40 epoxy vinyl ester and either initiatorVII or VIII. The initiator and accelerant concentrations used were thesame as those used in the dynamic thermal analysis. Initiators weremixed with the resin for 5 minutes at 1,000 RPM, and 19.77±5.68 mgsamples were loaded into the instrument within 119±21 seconds aftermixing. Resin samples with varying concentrations of initiator (rangingfrom 8.25×10⁻⁴ mol/g to 2.06×10⁻⁴ mol/g) and accelerant (ranging from4.13×10⁻⁴ mol/g to 1.65×10⁻³ mol/g) were evaluated by isothermal DSC at38° C. (body temperature) for 120 minutes. Samples weighing 25.43±9.89mg were prepared as above and loaded into the DSC within 98±21 secondsafter addition of the accelerant.

The initial rate of polymerization and degree of conversion withinitiators VII and VIII were dependent on both temperature andconcentration of initiator and accelerant (FIGS. 8A and 8B). Forexample, at 25° C., initiator VII exhibited hardly any conversion ofmonomer at the lower concentrations of initiator and accelerant (FIG.8B), while initiator VII exhibited almost 60% conversion after 2 hoursunder the same conditions. Determination of temperature andconcentration dependence is essential in determining whichinitiator/accelerant combination is most likely to initiatepolymerization of a specified monomer in situ before the monomer is lostby diffusion into the biological system. Since initiators IX, X and XIexhibited minimal reactivities, these isothermal experiments and thefollowing stoichiometric dependence experiments were only performed withinitiators VII and VIII.

Example 6 Reactivity of Initiators With Accelerants

Dynamic DSC experiments were used to determine the reactivity ofinitiators VII to XI with accelerants XII to XIV in the polymerizationof Derakane 510A-40 epoxy vinyl ester resin. The temperature rangeanalyzed was 25° C.-300° C., with a heating rate of 10° C./min. Theaccelerants were chosen to simulate the steric and electronic propertiesof accelerants tethered to the surface of HA particles. Two sets ofinitiator/accelerant combinations were analyzed—1) 4.13×10⁻⁴ mol/g resinof initiator and 8.25×10⁻⁵ mol/g resin of accelerant, and 2) 8.25×10⁻⁵mol/g resin of initiator and 4.13×10⁻⁴ mol/g resin of accelerant. Threetrials were performed for each combination of initiator and accelerant.Table 4 lists the average onset temperatures for each combination.

TABLE 4 Onset temperatures of polymerization using different types andconcentrations of initiators and accelerants Average Onset Temperature(° C.) Initiator Accelerant XII Accelerant XIII Accelerant XIV (4.13 ×10⁻⁴ mol/g) (8.25 × 10⁻⁵ mol/g) (8.25 × 10⁻⁵ mol/g) (8.25 × 10⁻⁵ mol/g)VII 61 37 36 VIII 92 71 65 IX 116 112 110 X 175 172 159 XI 136 135 127Initiator Accelerant XII Accelerant XIII Accelerant XIV (8.25 × 10⁻⁵mol/g) (4.13 × 10⁻⁴ mol/g) (4.13 × 10⁻⁴ mol/g) (4.13 × 10⁻⁴ mol/g) VII42 <25 <25 VIII 70 49 42 IX 116 101 61 X 170 163 151 XI 131 124 115

In general, the addition of accelerants either lowered, or had no effecton the onset temperature of polymerization. The onset temperature ofpolymerization with initiator VII was most affected by the addition ofaccelerant. As the concentration of initiator and accelerant increased,the onset temperature of polymerization decreased (Table 4). InitiatorVIII did not demonstrate a high level of reactivity with accelerant XIIat the lower concentration, as indicated by a minimal change in onsettemperature relative to thermal polymerization of the epoxy vinyl esterresin (compare Table 3 to Table 4). However, when the concentration ofinitiator VIII was increased two-fold and that of accelerant XII wasincreased five-fold, the onset temperature significantly decreased to70.1° C. In addition, initiators VII and VIII appeared to react betterwith accelerants XIII and XIV than with accelerant XII. This observationis consistent with increased nucleophilicity of the tertiary amine dueto donation of electron density from the methyl functionality in thepara position of the benzene ring of accelerant XIII byhyperconjugation. Similarly, accelerant XIV may demonstrate a higherlevel of reactivity with these initiators as a result of itsbifunctionality.

The average onset temperature for polymerization with initiator IXdecreased with the addition of accelerant, but did not decrease withincreased concentration of initiator IX and accelerant. Initiator Xboiled off in each evaluation except for when it was paired withaccelerant XIV, and onset temperature of polymerization did not changesignificantly with increasing concentration of initiator X andaccelerant. Similarly, initiator XI exhibited consistently high onsettemperatures of polymerization that were not affected by the additionand concentration of accelerant. These observations suggest thatinitiator X and XI may not be reactive enough for the system envisioned.

Example 7 Effect of Accelerant/Initiator Ratios on InitialPolymerization Rates

When a crack propagates through a self-healing bone cement based on freeradical polymerization, healing agents released into the crack plane maymix at less than desirable concentrations. Thus, in comparing initiatorsfor application in a self-healing system, the effect of stoichiometry onthe eventual polymerization was investigated. The polymerization of theepoxy vinyl ester resin at 38° C. was evaluated using a range ofaccelerant/initiator concentration ratios ([A]/[I]).

The ratio of [A]/[I] had a minimal effect on polymerizations initiatedby VII at lower concentrations of accelerant (lower ratios) (FIGS. 9Aand 9B). However, at higher [A]/[I] for initiator VII, polymerizationrate and degree of conversion decreased. Thus, as long as theconcentration of accelerant XII is not too high, it appears thatpolymerization in the crack plane will occur rapidly. This observationis consistent with the work of Vazquez and coworkers who demonstratedthat when accelerants are present at high concentrations, they can actas polymerization inhibitors (Vazquez, B.; Elvira, C.; Levenfeld, B.;Pasqual, B.; Goñi, I.; Gurruchaga, M.; Ginebra, M. P.; Gil, F. X.;Planell, J. L.; Liso, P. A.; Rebuelta, M.; San Roman, J., Journal ofBiomedical Materials Research 1997, 34, 129).

Optimal [A]/[I] ratios ranged from 0.50-2.98. Initial polymerizationrates for optimal stoichiometric concentrations of initiator VIII wereslower than for initiator VI (FIG. 9B). However, while the initial rateof polymerization and degree of conversion of initiator VII was observedto decrease significantly at [A]/[I]=8.00, initiator VIII did notdisplay as sharp a change in initial rate of polymerization and degreeof conversion at this concentration ratio. The rationale thatpolymerization must occur at a fast rate to avoid loss of monomer to thebiological system favors initiator VII over initiator VIII as acandidate for the system envisioned. On the other hand, when a crackruptures embedded microcapsules in a self-healing system, releasing itscontents into the crack plane, parameters such as viscosity, mixingissues, and varying rates of flow can cause the mixture in the crackplane to be at less than ideal stoichiometric concentrations. Thus, thefact that initiator VIII is less dependent upon the ratios of accelerantto initiator concentration could compensate for the slower initialpolymerization rates and lower degree of conversion observed inpolymerizations initiated with this initiator.

Example 8 Effect of Accelerant/Initiator Ratios on Mechanical Properties

The average moduli of resin samples cured with varying concentrations ofinitiators VII and VIII and accelerant XII were measured in three pointbend dynamic mechanical analysis (DMA) experiments. The type ofinitiator used, as well as the [A]/[I] ratio, did not appear to have asignificant effect on the modulus of the resulting polymerized resin. Onaverage, resins prepared with initiator VIII exhibited slightly loweraverage moduli than those prepared with initiator VII (FIG. 10). Whilethe modulus of samples prepared with initiator VIII reached a maximum atan [A]/[I] ratio of 1.33, a gradual increase was observed for samplesprepared with initiator VII, with the maximum average modulus occurringat an [A]/[I] ratio of 8.00. Overall, these results suggest that theaverage modulus is less dependent on the [A]/[I] ratio when initiatorVII is used as the initiator.

Example 9 Qualitative Monomer Reactivity Screening

Initiator VII (1 wt %, 2 wt %) and DMA (0.1 wt %, 0.5 wt %) were addedto 5 mL samples of monomer mixtures in 20 mL scintillation vials. Thecontents of the vials were stirred using a vortex. The samples weremonitored every 5 min for the first 30 min, followed by every hour up to4 h, then at 8 h, 12 h and 24 h. The physical characteristics of thesamples were observed and descriptions recorded at the times specified.

The screening experiments referred to here were qualitative and weresimply aimed at determining reactivity of the monomer or blend ofmonomers to a combination of BPO (1 wt % or 2 wt %) and DMA (0.1 wt % or0.5 wt %).

The results of these screening experiments have been summarized inTables 5-7. In general, most mixtures polymerized at the higherconcentration of initiator (2 wt %) and accelerant (0.5 wt %). Ethyleneglycol dimethacrylate (EGDMA) appeared to be the most versatile monomerat these concentrations of initiator and accelerant, yielding a hardcross-linked polymer in 4 h or less in all combinations with MMA, BMAand styrene.

TABLE 5 Copolymerization of Monomer III (Bis-GMA) Monomer Amount Time toAdded added (wt %) Polymerization Description of Polymer Bis-GMAExperiments: 1 wt % BPO and 0.1 wt % DMA added MMA 20 24 h incompletepolymerization MMA 30 24 h incomplete polymerization MMA 40  2 h hardpolymer MMA 50  4 h hard polymer MMA 60 N/A N/A MMA 70 N/A N/A MMA 80N/A N/A BMA 20 24 h incomplete polymerization BMA 30 24 h incompletepolymerization BMA 40 24 h incomplete polymerization BMA 50 24 hincomplete polymerization BMA 60 24 h incomplete polymerization BMA 70BMA 80 Styrene 20 24 h incomplete polymerization Styrene 30 24 hincomplete polymerization Styrene 40 24 h incomplete polymerizationStyrene 50 24 h incomplete polymerization Styrene 60 24 h incompletepolymerization Styrene 70 24 h hard polymer Styrene 80 24 h hard polymerBis-GMA Experiments: 2 wt % BPO and 0.5 wt % DMA added MMA 20 24 hincomplete polymerization MMA 30 30 min incomplete polymerization MMA 4030 min hard polymer MMA 50 30 min hard polymer MMA 60 30 min hardpolymer MMA 70 30 min hard polymer MMA 80 30 min hard polymer BMA 20 24h incomplete polymerization BMA 30 30 min incomplete polymerization BMA40 30 min incomplete polymerization BMA 50 30 min incompletepolymerization BMA 60 30 min incomplete polymerization BMA 70  2 h hardpolymer BMA 80  2 h hard polymer Styrene 20 24 h incompletepolymerization Styrene 30 30 min incomplete polymerization Styrene 40 30min incomplete polymerization Styrene 50 30 min incompletepolymerization Styrene 60  2 h incomplete polymerization Styrene 70  2 hhard polymer Styrene 80  2 h hard polymer

TABLE 6 Copolymerization of Monomer IV (TMPTMA) Monomer Amount Time toAdded added (wt %) Polymerization Description of Polymer TMPTMAExperiments: 1 wt % BPO and 0.1 wt % DMA added MMA 20 N/A N/A MMA 30 N/AN/A MMA 40 N/A N/A MMA 50 N/A N/A MMA 60 N/A N/A MMA 70 N/A N/A MMA 80N/A N/A BMA 20 N/A N/A BMA 30 N/A N/A BMA 40 N/A N/A BMA 50 N/A N/A BMA60 N/A N/A BMA 70 N/A N/A BMA 80 N/A N/A Styrene 20 N/A N/A Styrene 30N/A N/A Styrene 40 N/A N/A Styrene 50 N/A N/A Styrene 60 24 h incompletepolymerization Styrene 70 24 h incomplete polymerization Styrene 80 24 hincomplete polymerization TMPTMA Experiments: 2 wt % BPO and 0.5 wt %DMA added MMA 20 30 min hard polymer MMA 30 30 min hard polymer MMA 4030 min hard polymer MMA 50 30 min hard polymer MMA 60 30 min hardpolymer MMA 70 30 min hard polymer MMA 80 30 min hard polymer BMA 20 30min N/A BMA 30 30 min N/A BMA 40 30 min N/A BMA 50 24 h incompletepolymerization BMA 60 24 h incomplete polymerization BMA 70 24 hincomplete polymerization BMA 80 24 h incomplete polymerization Styrene20 30 min hard polymer Styrene 30 30 min hard polymer Styrene 40 30 minhard polymer Styrene 50  4 h N/A Styrene 60  4 h incompletepolymerization Styrene 70  4 h hard polymer Styrene 80  4 h hard polymer

TABLE 7 Copolymerization of Monomer V (EGDMA) Monomer Amount Time toAdded added (wt %) Polymerization Description of Polymer EGDMAExperiments: 1 wt % BPO and 0.1 wt % DMA added MMA 20 N/A N/A MMA 30 N/AN/A MMA 40 N/A N/A MMA 50 N/A N/A MMA 60 N/A N/A MMA 70 N/A N/A MMA 80N/A N/A BMA 20 N/A N/A BMA 30 N/A N/A BMA 40 N/A N/A BMA 50 N/A N/A BMA60 N/A N/A BMA 70 N/A N/A BMA 80 N/A N/A Styrene 20 N/A N/A Styrene 3024 h incomplete polymerization Styrene 40 24 h incomplete polymerizationStyrene 50 24 h incomplete polymerization Styrene 60 24 h incompletepolymerization Styrene 70 24 h incomplete polymerization Styrene 80 24 hincomplete polymerization EGDMA Experiments: 2 wt % BPO and 0.5 wt % DMAadded MMA 20 30 min hard polymer MMA 30 30 min hard polymer MMA 40 30min hard polymer MMA 50 30 min hard polymer MMA 60 30 min hard polymerMMA 70 30 min hard polymer MMA 80 30 min hard polymer BMA 20 30 min hardpolymer BMA 30 30 min hard polymer BMA 40 30 min hard polymer BMA 50 30min hard polymer BMA 60  2 h hard polymer BMA 70  2 h hard polymer BMA80  2 h hard polymer Styrene 20  2 h hard polymer Styrene 30  2 h hardpolymer Styrene 40  2 h hard polymer Styrene 50  2 h hard polymerStyrene 60  4 h hard polymer Styrene 70  4 h hard polymer Styrene 80  4h hard polymer

Example 10 Simulated Bone Cement Sample Preparation and Testing

Simulated samples of bone cement were prepared from two parts and werebased on the composition of Surgical Simplex® P. The solid part includeda total of 40 g of powder, of which 1.7 wt % was initiator VII, and theremainder was PMMA (MW=300,000 g/mol, Polysciences). The liquid part (20mL) included DMA (2.6 vol %), and the remainder was MMA. The two partswere mixed together, and the mixture was quickly transferred to a TDCBmold, which was made of either Delrin® or Teflon®. The samples wereallowed to cure at room temperature for 24 hours, after which they werepin-loaded to failure at 5 μms⁻¹ under displacement control. Afterfailure, a healing agent mixture (0.03 mL) was injected into the crackplane. The samples were allowed to heal at room temperature for 24 hoursbefore testing to failure again. Preliminary reference test results aresummarized in Table 8.

TABLE 8 Healing performance of bone cement mimic compositions AverageAverage Average Healing Multifunctional Multifunctional InitiatorAccelerant Peak Virgin Peak Healed Efficiency Monomer Monomer BPO (wt %)DMA (wt %) Fracture Fracture (η_(avg), %) N/A MMA 0 0 138.8 [19.3] 70.6[1.1] 47 N/A MMA 2 0.5 160.2 [21.2] 119.0 [13.1] 74 Bis-GMA MMA 0 0140.6 [9.5] 0 0 Bis-GMA MMA 2 0.5 163.5 [34.0 ] 96.8 59 Bis-GMA BMA 0 0140.6 [16.7] 0 0 Bis-GMA BMA 2 0.5 175.3 [14.0] 69.4 [6.5] 40

Reference tests performed by injecting MMA alone into the crack plane ofvirgin simulated bone cement TDCB samples exhibited an average healingefficiency of about 47%. Similar observations of crack healing have beenattributed to chain entanglement in the crack plane promoted by thesolvent-induced depression of the glass transition temperature (T_(g))in the crack plane (Wang, P.; Lee, S.; Harmon, J. P., Journal of PolymerScience, Part B: Polymer Physics 1994, 32, 1217). This phenomenon iscommonly referred to as solvent welding. The addition of initiator VII(2 wt %) and DMA (0.5 wt %) to the MMA injected into the crack plane ofvirgin simulated bone cement samples resulted in polymerization of theMMA in the crack plane and a corresponding increase in the healingefficiency to 74%. No solvent welding was observed for samples in whichBis-GMA/MMA or Bis-GMA/BMA mixtures were injected into the crack plane.However when BPO and DMA were added to these polymerizer mixtures at thesame concentrations as above, healing efficiencies of 59% and 40%respectively were observed. Though they exhibited lower healingperformance in reference tests, mixtures such as Bis-GMA/MMA are morelikely to be used as polymerizers than neat monomers such as MMA, asthey are expected to exhibit less volume shrinkage.

Example 11 Polymerizations with Reactants in Capsules

Capsules were prepared containing either monomer IV (alone or incombination with bisphenol-A acrylate), initiator VII, initiator VIII,or accelerant XII. Table 9 lists the compositions of these capsules.

TABLE 9 Capsule compositions Monomer Bisphenol-A Accelerant Active AgentInitiator VII Initiator VIII IV acrylate XII Solvent Initiator 9.9 wt %in PA 60 g PA Initiator 8.8 wt % in EPA 60 g EPA Initiator 4.3 wt % in60 g hexyl hexyl acetate acetate Monomer Pure IV 0 Monomer 36.0 g 12.0 g12.1 g EPA Accelerant 10 wt % in Dibutyl solvent phthalate

Monomer IV was mixed with the initiator capsules containing 9.9 wt %initiator VII in PA and with the accelerant capsules containing 10 wt %accelerant XII at various ratios, and each mixture was polymerized.Qualitative results are listed in Table 10.

TABLE 10 Polymerization of monomer IV with initiator and accelerantcapsules Initiator Accelerant Monomer (g) Capsules (g) Capsules (g)Result 0.976 0.108 0.012 poor 1.010 0.207 0.032 Good 0.993 1.04 0.54BEST 1.020 0.985 0.97 good

The monomer capsules containing pure monomer IV were mixed with theinitiator capsules containing 8.8 wt % initiator VII in EPA and with onesmall drop of DMPT accelerant, and each mixture was polymerized.Qualitative results are listed in Table 11.

TABLE 11 Polymerization of monomer capsules with initiator capsulesMonomer Initiator Capsules (g) Capsules (g) Result 0.26 0.14 Mostlyuncured, pockets of very dense polymer 0.55 0.13 Some uncured at edgesof film 1.05 0.11 Best adhesion, good film

While various embodiments of the invention have been described, it willbe apparent to those of ordinary skill in the art that other embodimentsand implementations are possible within the scope of the invention.Accordingly, the invention is not to be restricted except in light ofthe attached claims and their equivalents.

1. A composite material precursor composition, comprising: a matrixprecursor; a first plurality of capsules comprising a liquidpolymerizer; an activator, where the liquid polymerizer polymerizes whenin contact with the activator; and a plurality of functionalizedparticles comprising particles having a surface, and a functional groupimmobilized on the surface of the particles; where the functional groupcomprises an accelerant for the polymerization of the liquidpolymerizer.
 2. The composition of claim 1, where the liquid polymerizercomprises at least one of an acrylate monomer and an alkylacrylatemonomer, and the activator comprises a free-radical initiator.
 3. Thecomposition of claim 2, where the functional group comprises aN,N-dimethylaniline group.
 4. The composition of claim 3, where theparticles comprise hydroxyapatite.
 5. The composition of claim 4, wherethe liquid polymerizer comprises MMA, the initiator comprises BPO, andthe functionalized particles comprise dimethylaminobenzylalcohol-modified hydroxyapatite.
 6. The composition of claim 2, wherethe matrix precursor comprises a precursor for PMMA.
 7. The compositionof claim 2, where the liquid polymerizer comprises at least one monomerselected from the group consisting of MMA and BMA, and at least onemonomer selected from the group consisting of Bis-GMA, TMPTMA and EGDMA.8. The composition of claim 2, where the initiator comprises a peroxideinitiator.
 9. The composition of claim 2, further comprising activatorparticles comprising the initiator.
 10. A composite material,comprising: a solid polymer matrix; a first plurality of capsules in thesolid polymer matrix, the first plurality of capsules comprising aliquid polymerizer; an activator in the solid polymer matrix, where theliquid polymerizer polymerizes when in contact with the activator; and aplurality of functionalized particles in the solid polymer matrix, thefunctionalized particles comprising particles having a surface, and afunctional group immobilized on the surface of the particles, where thefunctional group comprises an accelerant for the polymerization of theliquid polymerizer in the solid polymer matrix.
 11. The compositematerial of claim 10, where the liquid polymerizer comprises at leastone of an acrylate monomer and an alkylacrylate monomer, and theactivator comprises a free-radical initiator.
 12. A method of making acomposite material, comprising: combining ingredients comprising amatrix precursor, a first plurality of capsules comprising a liquidpolymerizer, an activator, where the liquid polymerizer polymerizes whenin contact with the activator, and a plurality of functionalizedparticles comprising particles having a surface, and a functional groupimmobilized on the surface of the particles, where the functional groupcomprises an accelerant for the polymerization of the liquidpolymerizer; and solidifying the matrix precursor to form a solidpolymer matrix.
 13. The method of claim 12, where the functional groupcomprises a N,N-dimethylaniline group.
 14. The method of claim 12, wherethe particles comprise hydroxyapatite.
 15. The method of claim 12, wherethe liquid polymerizer comprises at least one monomer selected from thegroup consisting of MMA and BMA, and at least one monomer selected fromthe group consisting of Bis-GMA, TMPTMA and EGDMA.
 16. The method ofclaim 12, where the activator comprises a peroxide initiator.
 17. Thecomposite material of claim 10, where the functional group comprises aN,N-dimethylaniline group.
 18. The composite material of claim 10, wherethe particles comprise hydroxyapatite.
 19. The composite material ofclaim 10, where the liquid polymerizer comprises at least one monomerselected from the group consisting of MMA and BMA, and at least onemonomer selected from the group consisting of Bis-GMA, TMPTMA and EGDMA.20. The composite material of claim 10, where the activator comprises aperoxide initiator.